The prevalence of major depressive disorder (MDD) among patients with diabetes (DM) is twice that of the general population. The co-occurrence of MDD and DM is associated with hyperglycemia, increased diabetic complications and mortality, increased costs, as well as poorer adherence to a healthy diet and regular exercise. Despite early evidence that successful treatment of depression is associated with improvements in glycemic control, two of every three cases depression are left untreated by primary care physicians. Major societal benefits from basic and clinical research will not be realized unless translation of their findings to real-world practice occurs. Studies suggest that both effective depression treatment and disease self-management improve outcomes for diabetes, but to date studies have not used both approaches simultaneously. As part of our goal of translating research-based practice into real world settings we propose an innovative approach consisting of a comprehensive diabetes and depression intervention (CDDI), which combines a measurement-based pharmacological treatment algorithm for MDD with a nurse-supervised disease self-management program for both diabetes and MDD. CDDI is specifically designed to be incorporated into routine primary care practice making it more likely to be generalizable to real-world practice. The proposed pilot study involves a 32-week randomized controlled trial in primary care of a comprehensive diabetic and depression intervention (CDDI) in a group of patients with type 2 diabetes and comorbid MDD compared to a group treated with usual care for MDD plus disease self-management for diabetes (UC+DSMDM). A total of 48 patients will be enrolled in this pilot study at 2 primary care sites. The study will include a 16-week acute treatment phase followed by a 16-week follow-up phase. Overall Goal: To translate research-based treatment procedures that have been shown to improve outcomes for both DM and MDD for use in primary care. Specific aims: Aim 1: To evaluate the benefits of CDDI in improving diabetic outcomes compared to UC+DSM-DM. We expect greater improvement in overall HbA1c levels, diabetic quality of life (DQOL), and reduced diabetic symptom burden among patients assigned to CDDI. Aim 2: To evaluate the benefits of CDDI in improving depression outcomes compared to UC+DSM-DM. We expect superior clinical outcomes for depression in those assigned to the CDDI. Exploratory Aims: To evaluate the benefits of CDDI in terms of improved (1) cardiovascular risk factors (blood pressure, body mass index (BMI), lipids, &abdominal fat);(2) levels of exercise and better diet (as measured by the summary of diabetes self-care activities (SDSCA) measure);(3) clinician and patient satisfaction with care;(4) fidelity to treatment guidelines, and (5) cognitive function as determined by the Digit Symbol Coding Test (DSCT). PUBLIC HEALTH RELEVANCE: The presence of major depression in patients with diabetes is a significant public health burden, and is associated with high blood sugar (hyperglycemia), increased diabetic complications and mortality, increased costs, as well as poorer adherence to a healthy diet and regular exercise. As part of our goal of translating research-based practice into real world settings we propose an innovative approach consisting of a comprehensive diabetes and depression intervention (CDDI) taking place in primary care, which combines a medication treatment protocol for major depressive disorder (MDD) with a nurse-supervised disease selfmanagement program for both diabetes and depression. The major contribution of this proposal as health services research is to use our team's expertise to translate research-based treatment procedures that have been shown to improve outcomes for both diabetes and MDD for use in a primary care setting.